Notch controls the cell cycle to define leader versus follower identities during collective cell migration

  1. Zain Alhashem
  2. Dylan Feldner-Busztin
  3. Christopher Revell
  4. Macarena Alvarez-Garcillan Portillo
  5. Karen Camargo-Sosa
  6. Joanna Richardson
  7. Manuel Rocha
  8. Anton Gauert
  9. Tatianna Corbeaux
  10. Martina Milanetto
  11. Francesco Argenton
  12. Natascia Tiso
  13. Robert Kelsh
  14. Victoria E Prince
  15. Katie Bentley  Is a corresponding author
  16. Claudia Linker  Is a corresponding author
  1. King's College London, United Kingdom
  2. The Francis Crick Institute, United Kingdom
  3. University of Bath, United Kingdom
  4. The University of Chicago, United States
  5. University of Padova, Italy
  6. University of Chicago, United States

Abstract

Coordination of cell proliferation and migration is fundamental for life, and its dysregulation has catastrophic consequences, such as cancer. How cell cycle progression affects migration, and vice-versa, remains largely unknown. We address these questions by combining in-silico modelling and in vivo experimentation in the zebrafish Trunk Neural Crest (TNC). TNC migrate collectively, forming chains with a leader cell directing the movement of trailing followers. We show that the acquisition of migratory identity is autonomously controlled by Notch signalling in TNC. High Notch activity defines leaders, while low Notch determines followers. Moreover, cell cycle progression is required for TNC migration and is regulated by Notch. Cells with low Notch activity stay longer in G1 and become followers, while leaders with high Notch activity quickly undergo G1/S transition and remain in S-phase longer. In conclusion, TNC migratory identities are defined through the interaction of Notch signalling and cell cycle progression.

Data availability

The model code is accessible at https://github.com/Bentley-Cellular-Adaptive-Behaviour-Lab/NeuralCrestCpp. The code used to perform the LDA analysis is accessible in the supplementary files. All numerical data used in the figures is accessible in the supplementary data source file.

Article and author information

Author details

  1. Zain Alhashem

    Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8320-3836
  2. Dylan Feldner-Busztin

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Christopher Revell

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9646-2888
  4. Macarena Alvarez-Garcillan Portillo

    Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Karen Camargo-Sosa

    University of Bath, Bath, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Joanna Richardson

    Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2092-3876
  7. Manuel Rocha

    The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Anton Gauert

    Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3013-5374
  9. Tatianna Corbeaux

    Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Martina Milanetto

    Department of Biology, University of Padova, Padova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  11. Francesco Argenton

    Department of Biology, University of Padova, Padova, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0803-8236
  12. Natascia Tiso

    Department of Biology, University of Padova, Padova, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5444-9853
  13. Robert Kelsh

    University of Bath, Bath, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9381-0066
  14. Victoria E Prince

    University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Katie Bentley

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    katie.bentley@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  16. Claudia Linker

    Randall Centre for Cell and Molecular Biophysics, King's College London, London, United Kingdom
    For correspondence
    claudia.linker@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2028-6109

Funding

Medical Research Council (G1000080/1)

  • Zain Alhashem

Royal Society (2010/R1)

  • Zain Alhashem

Wellcome Trust (207630/Z/17/Z)

  • Zain Alhashem

Eucine Kennedy Shiver National Institute of Child Health & Human Development of the National Institues of Health (T32HD055164)

  • Manuel Rocha

Eucine Kennedy Shiver National Institute of Child Health & Human Development of the National Institues of Health (F31HD097957)

  • Manuel Rocha

Cancer Research UK (FC001751)

  • Dylan Feldner-Busztin

Medical Research Council (FC001751)

  • Dylan Feldner-Busztin

Wellcome Trust (FC001751)

  • Dylan Feldner-Busztin

Biotechnology and Biological Sciences Research Council (BB/S015906/1)

  • Robert Kelsh

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Tatjana Piotrowski, Stowers Institute for Medical Research, United States

Ethics

Animal experimentation: Zebrafish were maintained in accordance with UK Home Office regulations UK Animals (Scientific Procedures) Act 1986, amended in 2013 under project license P70880F4C.

Version history

  1. Preprint posted: May 27, 2021 (view preprint)
  2. Received: September 7, 2021
  3. Accepted: March 22, 2022
  4. Accepted Manuscript published: April 19, 2022 (version 1)
  5. Version of Record published: May 24, 2022 (version 2)

Copyright

© 2022, Alhashem et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Zain Alhashem
  2. Dylan Feldner-Busztin
  3. Christopher Revell
  4. Macarena Alvarez-Garcillan Portillo
  5. Karen Camargo-Sosa
  6. Joanna Richardson
  7. Manuel Rocha
  8. Anton Gauert
  9. Tatianna Corbeaux
  10. Martina Milanetto
  11. Francesco Argenton
  12. Natascia Tiso
  13. Robert Kelsh
  14. Victoria E Prince
  15. Katie Bentley
  16. Claudia Linker
(2022)
Notch controls the cell cycle to define leader versus follower identities during collective cell migration
eLife 11:e73550.
https://doi.org/10.7554/eLife.73550

Share this article

https://doi.org/10.7554/eLife.73550

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